Multimodal investigation of melanopsin retinal ganglion cells in Alzheimer's disease

Objective: In Alzheimer's disease (AD), the presence of circadian dysfunction is well-known and may occur early in the disease course. The melanopsin reti-nal ganglion cell (mRGC) system may play a relevant role in contributing to circadian dysfunction. In this study, we aimed at evaluating, through a multi-modal approach, the mRGC system in AD at an early stage of disease. Methods: We included 29 mild-moderate AD (70.9 111 years) and 26 (70.5 18 years) control subjects. We performed an extensive neurophtalmolo-gical evaluation including optical coherence tomography with ganglion cell layer segmentation, actigraphic evaluation of the rest-activity rhythm, chromatic pupillometry analyzed with a new data-fitting approach, and brain functional MRI combined with light stimuli assessing the mRGC system. Results: We demonstrated a significant thinning of the infero-temporal sector of the gan-glion cell layer in AD compared to controls. Moreover, we documented by acti-graphy the presence of a circadian-impaired AD subgroup. Overall, circadian measurements worsened by age. Chromatic pupillometry evaluation highlighted the presence of a pupil-light response reduction in the rod condition pointing to mRGC dendropathy. Finally, brain fMRI showed a reduced occipital cortex activation with blue light particularly for the sustained responses. Interpreta-tion: Overall, the results of this multimodal innovative approach clearly docu-ment a dysfunctional mRGC system at early stages of disease as a relevant contributing factor for circadian impairment in AD providing also support to the use of light therapy in AD.

Automated summary

This study aimed to evaluate the melanopsin retinal ganglion cell (mRGC) system in early stages of Alzheimer's disease (AD) using a multi-modal approach. The results showed dysfunction of the mRGC system in AD patients, which may contribute to circadian impairment.